Asparagine synthetase (ASNS) catalyzes the biosynthesis of L-asparagine from L-aspartate in an ATP-dependent reaction for which L-glutamine is used as a nitrogen source in vivo [Non Patent Literature 1]. Accordingly, L-asparagine is not an essential amino acid that must be obtained from outside of the body. If the supply of L-asparagine is decreased in normal cells, it can be compensated by the synthesis of L-asparagine. However, in the case of lymphoblasts, since the activity of ASNS is not sufficient therein, L-asparagine must be obtained from outside [Non Patent Literature 2]. L-asparaginase (ASNase) is an enzyme that hydrolyzes L-asparagine into L-aspartate and ammonia [Non Patent Literature 3], and it is an important drug for the treatment of many cases of acute lymphatic leukemia (ALL). Administration of ASNase causes depletion of L-asparagine in blood, spinal fluid and bone marrow, and it also causes depletion of L-asparagine in cells. Lymphoblast cells with an extremely low ASNS level are susceptible to cell death. In an in-vivo system, the exposure of lymphoblast cells to ASNase terminated the G1 phase and caused apoptosis [Non Patent Literature 4]. It has been demonstrated that overexpression of human ASNS is sufficient for inducing ASNase resistance [Non Patent Literature 5]. The relationship between the expression level of ASNS and sensitivity to ASNase has been observed not only in leukemia cells, but also in ovarian cancer cells [Non Patent Literatures 6 and 7]. These findings suggest the importance of the monitoring of ASNS activity as a diagnostic marker for determining treatment with ASNase. Although the relationship between ASNase resistance and the expression level of ASNS mRNA has been widely reported [Non Patent Literature 8], there have been a few number of studies in which the amount of ASNS protein in human leukemia has been determined [Non Patent Literatures 9-13]. Such a few numbers of reports include a report stating the importance of ASNS protein measurement for the estimation of sensitivity to ASNase [Non Patent Literature 13].
A baculovirus expression system using the insect cell line Sf9 as a host has been used for large scale production of protein. In particular, many researchers including ourselves have demonstrated that a fusion protein with a membrane protein or a virus gp64 protein can be displayed not only on a Sf9 cell, but also on a budded baculovirus (BV) particle. Accordingly, an exogenous protein displayed on BV can be used for immunization, without purification of an antigenic protein [Non Patent Literatures 14, 15, and 16].